Yuvraj Singh proved the difference between the two sides as India kept alive their hopes of a semi-final spot at the World Twenty20.
The left-hander hit six sixes off Stuart Broad in the penultimate over of the India innings, propelling their total to an impressive 218-4 - one that always looked beyond England.
Remarkably, England's score of 171-5 after 18 overs was the same as India's had been at the same stage - for the loss of two fewer wickets - but Yuvraj's remarkable over could not be matched by his counterparts.
It was the first maximum score from an over in international Twenty20 cricket and ultimately left England winless in three second phase games.
Openers Gautam Gambhir and Virender Sehwag set the tone with a partnership of 136, Sehwag the first to reach his half-century from 38 balls while Gambhir took longer, but had faced just 36 deliveries when he got there a few overs later.
Sehwag - who re-dedicated himself to the game after being left out of this summer's tour of England - looked in great nick as he used his favourite cover drive to full effect.
They were 90-0 at the halfway mark but it was only a precursor to what was to follow.
Sehwag tried one shot too many having made 68, being bowled trying to clip the ball to the leg side, before Gambhir swept Darren Maddy to Broad at short fine leg having just started to look very dangerous.
Robin Uthappa was dismissed by Tremlett soon after to bring in Yuvraj, another player forced to sit out the Tests against England.
The left-hander was straight into action, driving Flintoff for four, after which the pair shared some choice words.
The contretemps clearly got the batsman's blood up, as he cut, drove, clubbed and slogged six maximums off the luckless Broad in the penultimate over, taking his score to 50 from 12 balls and his side's total past 200.
Flintoff sent down the final over and Yuvraj drove him over extra cover for another six before holing out to Collingwood at long-on - but the damage was done.
England were game in reply, plucky knocks from Maddy (29 from 20 balls), Vikram Solanki (43 off 31) and Kevin Pietersen (39 from 23) giving them some hope of a consolation win.
But some accurate bowling from RP Singh and Harbhajan Singh choked the runs, and when Owais Shah (21 from 13) and Collingwood (28 off 20) fell in the same RP Singh over the game was up.
England eventually reached 200-6 after some lusty blows from Luke Wright but they leave South Africa with plenty on their mind - India on the other hand must beat South Africa on Thursday to have a chance of progressing.